This invention relates to pyridines substituted at the 4-position with a thioether and carboxy, (C.sub.2 -C.sub.5)carboalkoxy or formyl containing side chain, and the pharmaceutically acceptable salts thereof, having utility in the treatment of arthritis as well as utility as intermediates for the preparation of the corresponding alcohols having the same utility.
A number of compounds have been known in the art to be useful as antiinflammatory agents, for example the corticosteroids, phenylbutazone, indomethacin, piroxicam and other benzothiazine dioxides (Lombardino, U.S. Pat. No. 3,591,584), 2-oxo-2,3-dihydrobenzofuran-3-carboxamides (Kadin, U.S. Pat. No. 3,676,463), and substituted diarylimidazoles (Lombardino, U.S. Pat. No. 3,707,475). Accordingly these compounds have therapeutic value in the treatment of arthritic and other inflammatory conditions. Such conditions have also been treated by administration of immunoregulatory agents, such as levamisole, as described, for example, in Arthritis and Rheumatism, 20, 1445 (1977) and Lancet, 1, 393 (1976). In efforts to find new and improved therapeutic agents for the treatment of these conditions, it has now been found that the novel pyridines of the present invention are active either as antiinflammatory agents or as regulants of the immune response in mammals, and in many cases, possess both types of activity. Because these activities are complementary, the latter are of particular value in the treatment of rheumatoid arthritis and other conditions where relief of the inflammation and regulation of the immune response is desired.
Not all of the compounds of the present invention are novel. Thus, acids and esters of the formula (I) wherein n=1 and Z=hydroxy or (C.sub.1 -C.sub.4)alkoxy have been disclosed as compounds useful as intermediates in the preparation of cephalosporin derivatives, British Patent Specification No. 1,434,271 (1976); specifically described are 2-(4-picolylthio)acetic acid and methyl 2-(4-picolylthio)acetate. Isomeric 2-(3-carboxypropylthiomethyl)pyridine and the corresponding alkyl ester derivatives have also been reported (British Patent Specification No. 1,213,049); the latter compounds are claimed to be useful for treating inflammation in non-human animals, but may well be devoid of the desirable immunoregulatory activity of the present compounds, since the derived alcohols are devoid of such activity at a level where alcohols derived from the present compounds have a high level of activity.